Photostabilizing compounds, compositions, and methods

ABSTRACT

Heterocyclic compounds are provided. In particular, the heteroatom of the heterocyclic compound may be nitrogen. The heterocyclic compounds may demonstrate capacity of stabilizing photoactive compounds. Topical compositions comprising these heterocyclic compounds are also provided. In particular, these topical compositions further comprise photoactive compounds. Methods for stabilizing photoactive compounds are also provided. These methods comprise mixing the photoactive compounds with photostabilizing heterocyclic compounds.

RELATED APPLICATIONS

This application claims priority from provisional patent applicationSer. No. 62/686,274 filed on Jun. 18, 2018.

TECHNICAL FIELD

The disclosure is in the field of compounds that stabilize chemicalsunscreens or other compounds that are photoactive, and relatedcompositions and methods.

BACKGROUND OF THE DISCLOSURE

Photoactive compounds are widely used. For example, sunscreens arephotoactive compounds. The most widely used UVA and UVB filters insunscreens are Avobenzone (butyl methoxydibenzoylmethane) and Octoxinate(ethylhexyl methoxycinnamate). While effective in blocking UVA and UVBrays respectively, upon exposure to UV light both Avobenzone andOctinoxate are subject to degradation. Upon exposure to UV lightOctinoxate will sometimes form dimers with other Octinoxate molecules.These dimers no longer absorb UVB and UVB efficacy is lost. Octinoxatewill also react with the double bond of the dominant form of Avobenzoneresulting in the formation of cyclobutane which then forms ring openingstructures. The result is loss of UVA efficacy.

Retinoids are also photoactive compounds. Upon exposure to UV light,retinoids are subject to photoreactions, such as photoisomerization,photopolymerization, photooxidation, and photodegradation. The resultedphotodecomposition products do not have the same level of biologicalactivities. The result is loss of biological efficacy.

Photostabilizers such as N-cyanodiphenylacrylates such as Octocrylene(2-Cyano-3,3-Diphenyl Acrylic Acid, 2-Ethylhexyl Ester) are known toinhibit the UV-induced photo degradation of Avobenzone. When Avobenzoneabsorbs a photon of UV light its electron enters a triplet energy state,which can lead to the photo-degradation of the Avobenzone. Octocryleneis able to accept the triplet excited state energy and return theAvobenzone to its original unexcited state. However, when Octoxinate ispresent, it sometimes will accept the triplet excited state energy fromAvobenzone and then react with the double bond found in the dominantform of Avobenzone. Accordingly, Octocrylene is sometimes, but notalways, effective for its intended purpose.

The problem of solving the instability of photoactive compounds iscritical. Sunscreens like Avobenzone and Octinoxate are widely used.Particularly, Avobenzone is one of the only UVA sunscreens approved forglobal use in sunscreen products. Also, retinoids are highly desired dueto their biological benefits and efficacies. Particularly, retinol is animportant regulator in epidermal cell growth, normal celldifferentiation, and cell maintenance.

The disclosure is directed to heterocyclic compounds, compositionscomprising those heterocyclic compounds, and related methods forstabilizing photoactive compounds that may include chemical sunscreens,such as Avobenzone or Octinoxate in particular, as well as otherunstable compounds such as retinol.

SUMMARY OF THE DISCLOSURE

The disclosure is directed to heterocyclic compounds having a structureaccording to Formula I:

In one embodiment, each of A¹, A², A³, A⁴, A⁵, A⁶, A⁷, and A⁸ isindependently selected from the group consisting of CR³ and N.

In one aspect, R³ is selected from the group consisting of H, OH, astraight or branched chain alkyl group having from about 1 to about 20carbon atoms, an alkoxy group having from about 1 to about 20 carbonatoms, an alkenyl group having from about 2 to about 20 carbon atoms, analkynyl group having from about 2 to about 20 carbon atoms, and an arylgroup having from about 6 to about 20 carbon atoms. Preferably, R³ isselected from H, a straight or branched chain alkyl group having fromabout 1 to about 20 carbon atoms, an alkoxy group having from about 1 toabout 20 carbon atoms. More preferably, R³ is selected from H, astraight or branched chain alkyl group having from about 1 to about 20carbon atoms. Most preferably, R³ is selected from the group consistingof H, and a straight or branched chain alkyl selected from the groupconsisting of methyl, ethyl, propyl, butyl, 2-methyl-1-propyl,2-methyl-2-propyl, pentyl, 2-methyl-2-butyl, hexyl, heptyl, octyl,decyl, or dodecyl.

In one alternative embodiment, each of A¹, A², A³, A⁴, A⁵, A⁶, A⁷, andA⁸ is independently selected from the group consisting of CH and N.

In one embodiment, at least one of A¹, A², A³, A⁴, A⁵, A⁶, A⁷, and A⁸ isN. In another embodiment, no more than four of A¹, A², A³, A⁴, A⁵, A⁶,A⁷, and A⁸ are N.

In one embodiment, each of B¹ and B² is independently selected from thegroup consisting of carbonyl or C═C(R¹)R².

In one alternative embodiment, each of R¹ and R² is independentlyselected from the group consisting of CN, C(═O)OR⁴. In one aspect, R¹and R² are not both CN. In one aspect, at least one of R¹ and R² isC(═O)OR⁴.

In one alternative aspect, R⁴ selected from the group consisting of H, astraight or branched chain alkyl group having from about 1 to about 20carbon atoms, an alkenyl group having from about 2 to about 20 carbonatoms, an alkynyl group having from about 2 to about 20 carbon atoms,and an aryl group having from about 6 to about 20 carbon atoms.Preferably, R⁴ is a straight or branched chain alkyl group having fromabout 1 to about 20 carbon atoms. More preferably, R⁴ is a straight orbranched chain alkyl group having at least 8, no more than 12 carbonatoms. Most Preferably, R⁴ is a straight or branched chain alkyl grouphaving 8 carbon atoms.

In one embodiment, examples of the compounds include, but not limit to,Compound 1-10.

The disclosure is also directed to compositions comprising at least oneheterocyclic compound having a structure according to Formula I.

In one embodiment, the composition comprises the heterocyclic compoundspresent in amount ranging from 0.01 to 25% by weight of the totalcomposition. Preferably, the heterocyclic compounds are present in thecomposition in amount ranging from 0.05 to 15% by weight of the totalcomposition. More preferably, the heterocyclic compounds are present inthe composition in amount ranging from 0.1 to 5% by weight of the totalcomposition.

In one embodiment, the composition further comprises at least onephotoactive compound. Preferably, the photoactive compound is selectedfrom the group consisting of a retinoid, a sunscreen, or mixturethereof.

In one aspect, the photoactive compound is a retinoid. Preferably, theretinoid is retinol.

In one aspect, the retinoid is present in amount ranging from about0.0001 to about 20% by weight of the total composition. Preferably, theretinoid is present in amount ranging from about 0.001 to about 10% byweight of the total composition. More preferably, the retinoid ispresent in amount ranging from about 0.01 to about 8% by weight of thetotal composition. Most preferably, the retinoid is present in amountranging from about 0.05 to about 5% by weight of the total composition.

In one aspect, the photoactive compound is a sunscreen. Preferably, thesunscreen is selected from the group consisting of a UVA chemicalsunscreen, a UVB chemical sunscreen, a physical sunscreen, and mixturethereof.

In one alternative aspect, the sunscreen is a UVA chemical sunscreen.Preferably, the UVA chemical sunscreen is selected from a groupconsisting of a dibenzoylmethane compound and a dicamphor sulfonic acidderivative. More preferably, the UVA chemical sunscreen is selected froma group consisting of dibenzoylmethane compounds. Examples of thedibenzoylmethane compounds include, but not limit to,4-methyldibenzoylmethane, 2-methyldibenzoylmethane,4-isopropyldibenzoylmethane, 4-tert-butyldibenzoylmethane,2,4-dimethyldibenzoylmethane, 2,5-dimethyldibenzoylmethane,4,4′diisopropylbenzoylmethane, 4-tert-butyl-4′-methoxydibenzoylmethane,4,4′-diisopropylbenzoylmethane,2-methyl-5-isopropyl-4′-methoxydibenzoymethane,2-methyl-5-tert-butyl-4′-methoxydibenzoylmethane. Most preferably, theUVA chemical sunscreen is Avobenzone.

In one alternative aspect, the UVA chemical sunscreen is present inamount ranging from about 0.001 to about 20% by weight of the totalcomposition. Preferably, the UVA chemical sunscreen is present in amountranging from about 0.005 to about 5% by weight of the total composition.More preferably, UVA chemical sunscreen is present in amount rangingfrom about 0.005 to about 3% by weight of the total composition.

In one alternative aspect, the UVA chemical sunscreen is Avobenzone andis present at not greater than about 3% by weight of the totalcomposition.

In one alternative aspect, the sunscreen is a UVB chemical sunscreen.Preferably, the UVB chemical sunscreen is selected from the groupconsisting of an alpha-cyano-beta, beta-diphenyl acrylic acid ester, abenzylidene camphor derivative, a cinnamate derivative, a benzophenonederivative, a menthyl salicylate derivative, an amino benzoic acidderivative, a salicylate derivative, and an ester of 2-phenyl ethanoland benzoic acid. More preferably, the UVB chemical sunscreen isselected from the group consisting of Octocrylene, 4-methylbenzylidenecamphor, Octinoxate, Cinoxate, Benzophenone 3, Sulisobenzone,Sulisobenzone Sodium, Homosalate, ethyl hexyl dimethyl PABA,ethyldihydroxypropyl PABA, octyl salicylate, TEA-salicylate,DEA-salicylate, phenyethyl benzoate. More preferably, the UVB chemicalsunscreen is selected from the group consisting of Octocrylene,4-methylbenzylidene camphor, Octinoxate, Benzophenone 3, Homosalate,ethyl hexyl dimethyl PABA, octyl salicylate. Most preferably, the UVBchemical sunscreen is Octinoxate.

In one alternative aspect, the UVB chemical sunscreen is present inamount ranging from about 0.001 to about 45% by weight of the totalcomposition. Preferably, the UVB chemical sunscreen is present in amountranging from about 0.005 to about 40% by weight of the totalcomposition. More preferably, UVA chemical sunscreen is present inamount ranging from about 0.01 to about 35% by weight of the totalcomposition.

In one aspect, the composition is a sunscreen composition. Preferably,the sunscreen composition has a SPF value ranging from about 1 to about50. More preferably, the sunscreen composition has a SPF value rangingfrom about 2 to about 45. Most preferably, the sunscreen composition hasa SPF value ranging from about 5 to about 30.

The disclosure is also directed to methods for stabilizing a photoactivecompound, comprising mixing the photoactive compound with at least oneheterocyclic compound having a structure according to Formula I.

In one embodiment, the photoactive compound is selected from a groupconsisting of Avobenzone, Octinoxate, retinol, or mixtures thereofagainst photo degradation due to exposure to UV light.

DETAILED DESCRIPTION

Photostabilizing compounds are highly desired. In some embodiments, thepresent disclosure relates to photostabilizing compounds having thecapability to stabilize photoactive compounds.

Each electron in one molecule has two possible spin states. When twoelectrons of a molecule are at the same molecular orbit and haveopposite spin states, these two electrons form an electron pair. Whenall electrons of a molecule are paired, this molecule is at a singletstate because the electronic energy levels of this molecule would notsplit when exposed into a magnetic field. When a molecule has only oneunpaired electron, this molecule is at a doublet state because theelectronic energy levels of this molecule may split into two levels whenexposed into a magnetic field. When a molecule has two unpairedelectrons whose spin states are parallel to each other, this molecule isat a triplet state because the electronic energy levels of this moleculemay split into three levels when exposed into a magnetic field.

In some embodiments, all electrons of the photoactive compound arepaired at the ground state.

In some embodiments, upon exposure to visible light and/or UV light, thephoton absorption of the photoactive compound may cause electronexcitation. In some alternative embodiments, upon excitation, anelectron of one electron pair may be promoted from the lower energyground state to a higher energy excited state. The electron pair may beunpaired, with one electron at the excited state and another at theground state. In one aspect, the excited electron may not change thespin orientation, and keeps the spin orientation opposite to the spinorientation of the other unpaired electron. This excited molecule is ata singlet excited state. In another aspect, the excited electron changesits spin orientation, which becomes parallel to the spin orientation ofthe other unpaired electron. This excited molecule is at a tripletexcited state.

In some embodiments, the photoactive compounds may become less stableupon being excited, subject to photochemical reactions that are mostlyirreversible. After undergoing these irreversible reactions, thephotoactive compounds generally lose their desired properties andefficacies. Because many photoactive compounds are widely used in theindustry due to their great properties and efficacies, it is critical tofind a way of stabilizing photoactive compounds.

In some embodiments, the photostabilizing compounds may stabilizephotoactive compounds. In one aspect, the photostabilizing compounds maybe capable of directly or indirectly assisting the energy transfer fromthe excited photoactive compounds. In one alternative aspect, theexcited photoactive compounds may be less likely to undergophotochemical reactions as they may more likely get back to their morestable states (i.e., the ground state) before undergoing photochemicalreactions due to the co-existing photostabilizing compounds. By loweringthe possibility that the photoactive compounds undergo irreversiblephotochemical reactions after being excited, the photostabilizingcompounds may effectively stabilize photoactive compounds.

A. The Compounds

How photostabilizing compounds assist the energy transfer from theexcited photoactive compounds is not well understood.

In some embodiments, the present disclosure relates to heterocycliccompounds. A heterocyclic compound is one that contains at least a ringmade up of more than one kind of atom. In one preferred aspect, theheterocyclic compound may be conjugated.

In one aspect, the heterocyclic compound may be aromatic, non-aromatic,or anti-aromatic. Preferably, the heterocyclic compound may be aromatic.

In one aspect, the heteroatom of the heterocyclic compound may benitrogen, oxygen, and/or sulfur. In a heterocyclic compound, aheteroatom is the atom in a ring that is not a carbon atom. Preferably,the heteroatom of the heterocyclic compound may be nitrogen.

Nitrogen as the heteroatom may affect the properties of heterocycliccompounds in various ways. Nitrogen is more electronegative than carbonis. That is, nitrogen has the higher tendency to attract a bonding pairof electrons than the tendency that carbon has. Also, Nitrogen has alone pair of electrons that may not form a bond with other atoms.

In one aspect, the nitrogen's lone pair may be on a p orbitalperpendicular to the heterocyclic ring. In this case, nitrogen may actas an electron donor to π orbitals of the heterocyclic system. Inanother aspect, the nitrogen's lone pair may be on a sp² hybrid orbitand lie outside the heterocyclic ring. In this case, nitrogen may act asan electron acceptor of the a orbitals of the heterocyclic systembecause it is more electron negative than carbon. The molecularelectronic structure of the heterocyclic compound may changedramatically when the number of the nitrogen atom(s) and the position(s)of nitrogen atom(s) change. The photophysical and photochemicalproperties of the heterocyclic compound may change according to thechanges of its molecular electronic structure. By carefully choosing thenumber of nitrogen atom(s) on the ring and the position(s) of nitrogenatom(s), desired photophysical and photochemical properties of thecompounds may be achieved.

In some embodiments, the disclosure is related to heterocyclic compoundshaving the structure according the Formula I:

In one embodiment, each of A¹, A², A³, A⁴, A⁵, A⁶, A⁷, and A⁸ isindependently selected from the group consisting of CR³ and N.

In one aspect, R³ is selected from the group consisting of:

(i) H;

(ii) OH;

(iii) a straight or branched chain alkyl group having from about 1 toabout 20 carbon atoms, preferably having from about 1 to about 10 carbonatoms, more preferably having from about 1 to about 6 carbon atoms; inone alternative aspect, the alkyl group is a straight or branched chainalkyl selected from the group consisting of methyl, ethyl, propyl,butyl, 2-methyl-1-propyl, 2-methyl-2-propyl, pentyl, 2-methyl-2-butyl,hexyl, heptyl, octyl, decyl, or dodecyl;

(iv) an alkoxy group having from about 1 to about 20 carbon atoms,preferably having from about 1 to about 12 carbon atoms, more preferablyhaving from about 1 to about 6 carbon atoms, most preferably the alkoxygroup is selected from the group consisting of methoxy, ethoxy, propoxy,butoxy;

(v) an alkenyl group having from about 2 to about 20 carbon atoms,preferably having from about 2 to about 12 carbon atoms, more preferablyhaving from about 2 to about 6 carbon atoms, most preferably the alkenylgroup is selected from the group consisting of vinyl, allyl,cyclopentenyl, hexenyl;

(vi) an alkynyl group having from about 2 to about 20 carbon atoms,preferably having from about 2 to about 12 carbon atoms, more preferablyhaving from about 2 to about 6 carbon atoms;

(vii) an aryl group having from about 6 to about 20 carbon atoms,preferably having from about 6 to about 14 carbon atoms, more preferablyhaving from about 6 to about 12 carbon atoms.

In one preferred aspect, R³ is selected from H; and a straight orbranched chain alkyl group having from about 1 to about 20 carbon atoms,preferably having from about 1 to about 10 carbon atoms, more preferablyhaving from about 1 to about 6 carbon atoms; in one alternative aspect,the alkyl group is a straight or branched chain alkyl selected from thegroup consisting of methyl, ethyl, propyl, butyl, 2-methyl-1-propyl,2-methyl-2-propyl, pentyl, 2-methyl-2-butyl, hexyl, heptyl, octyl,decyl, or dodecyl.

In one alternative embodiment, each of A¹, A², A³, A⁴, A⁵, A⁶, A⁷, andA⁸ is independently selected from the group consisting of CH and N.

In one embodiment, at least one of A¹, A², A³, A⁴, A⁵, A⁶, A⁷, and A⁸ isN. In one embodiment, no more than four of A¹, A², A³, A⁴, A⁵, A⁶, A⁷,and A⁸ are N.

In one embodiment, each of B¹ and B² is independently selected from thegroup consisting of carbonyl or C═C(R¹)R².

In one alternative embodiment, each of R¹ and R² is independentlyselected from the group consisting of CN, C(═O)OR⁴. In one aspect, R¹and R² are not both CN. In one aspect, at least one of R¹ and R² isC(═O)OR⁴.

In one aspect, R⁴ is selected from the group consisting of

(i) H;

(ii) a straight or branched chain alkyl group having from about 1 toabout 20 carbon atoms, preferably having from about 8 to about 12 carbonatoms, more preferably having from about 8 carbon atoms; in onealternative aspect, the alkyl group is a straight or branched chainalkyl selected from the group consisting of methyl, ethyl, propyl,butyl, 2-methyl-1-propyl, 2-methyl-2-propyl, pentyl, 2-methyl-2-butyl,hexyl, heptyl, octyl, decyl, or dodecyl, preferably a straight orbranched octyl group;

(iii) an alkenyl group having from about 2 to about 20 carbon atoms,preferably having from about 2 to about 12 carbon atoms, more preferablyhaving from about 2 to about 6 carbon atoms, most preferably the alkenylgroup is selected from the group consisting of vinyl, allyl,cyclopentenyl, hexenyl;

(iv) an alkynyl group having from about 2 to about 20 carbon atoms,preferably having from about 2 to about 12 carbon atoms, more preferablyhaving from about 2 to about 6 carbon atoms;

(v) an aryl group having from about 6 to about 20 carbon atoms,preferably having from about 6 to about 14 carbon atoms, more preferablyhaving from about 6 to about 12 carbon atoms.

In one preferred aspect, R⁴ is selected from H; a straight or branchedchain alkyl group having from about 1 to about 20 carbon atoms,preferably having from about 1 to about 10 carbon atoms; in onealternative aspect, the straight or branched chain alkyl group isselected from the group consisting of methyl, ethyl, propyl, butyl,2-methyl-1-propyl, 2-methyl-2-propyl, pentyl, 2-methyl-2-butyl, hexyl,heptyl, octyl, decyl, or dodecyl; in one preferred alternative aspect,the straight or branched chain alkyl group is a straight or branchedoctyl group.

By carefully selecting R³, the photophysical and photochemicalproperties of the heterocyclic compounds may be further optimized.

By carefully selecting R³ and R⁴, the hydrophilicity and/orlipophilicity of the heterocyclic compounds may be optimized. Thehydrophilicity and/or lipophilicity of the compounds may play animportant role in formulating the compositions comprising theheterocyclic compounds.

Specific, non-limiting examples of heterocyclic compounds are provided:

B. The Compositions

In some embodiments, the compositions of the disclosure may be topicalcompositions. In one aspect, the topical compositions may be in the formof solids, liquids, or gels. In one aspect, the topical compositions maybe aqueous based or anhydrous. Aqueous based compositions may be in theform of emulsions, solutions, or dispersions.

In some embodiments, the compositions comprise at least one heterocycliccompound having the structure according to Formula I. In one aspect, thecompound of Formulas I may be present in amounts ranging from about 0.01to about 25%, preferably about 0.05 to about 15%, more preferably fromabout 0.1 to about 5% by weight of the total composition.

In some embodiments, the topical compositions may further comprisecertain esters of 2-phenyl ethanol and benzoic acid. One example isphenethyl benzoate, which is sold under the tradename X-Tend 226®, byAshland.

In some embodiments, the topical compositions may further contain oils,waxes, thickening agents, vitamins, preservatives, antioxidants,botanical extracts, chemical or physical sunscreens or otheringredients.

In some preferred embodiments, the compositions comprise at least onephotoactive compound.

In one aspect, the photoactive compounds are retinoids and derivativesthereof. Preferably, the compositions comprise retinyl palmitate,retinol, retinoic acid, and/or Vitamin A in the form of beta carotene.

In one aspect, the retinoid is present in amount ranging from about0.0001 to about 20% by weight of the total composition. Preferably, theretinoid is present in amount ranging from about 0.001 to about 10% byweight of the total composition. More preferably, the retinoid ispresent in amount ranging from about 0.01 to about 8% by weight of thetotal composition. Most preferably, the retinoid is present in amountranging from about 0.05 to about 5% by weight of the total composition.

In one aspect, the photoactive compounds is sunscreen. Such sunscreensinclude chemical UVA or UVB sunscreens or physical sunscreens.

1. UVA Chemical Sunscreens

If desired, the composition may comprise one or more UVA sunscreens. Theterm “UVA sunscreen” means a chemical compound that blocks UV radiationin the wavelength range of about 320 to 400 nm. Preferred UVA sunscreensare dibenzoylmethane compounds having the general formula:

wherein R₁ is H, OR and NRR wherein each R is independently H, C₁₋₂₀straight or branched chain alkyl; R₂ is H or OH; and R₃ is H, C₁₋₂₀straight or branched chain alkyl.

Preferred is where R₁ is OR where R is a C₁₋₂₀ straight or branchedalkyl, preferably methyl; R₂ is H; and R₃ is a C₁₋₂₀ straight orbranched chain alkyl, more preferably, butyl.

Examples of suitable UVA sunscreen compounds of this general formulainclude 4-methyldibenzoylmethane, 2-methyldibenzoylmethane,4-isopropyldibenzoylmethane, 4-tert-butyldibenzoylmethane,2,4-dimethyldibenzoylmethane, 2,5-dimethyldibenzoylmethane,4,4′diisopropylbenzoylmethane, 4-tert-butyl-4′-methoxydibenzoylmethane,4,4′-diisopropylbenzoylmethane,2-methyl-5-isopropyl-4′-methoxydibenzoymethane,2-methyl-5-tert-butyl-4′-methoxydibenzoylmethane, and so on.Particularly preferred is 4-tert-butyl-4′-methoxydibenzoylmethane, alsoreferred to as Avobenzone. Avobenzone is commercially available fromGivaudan-Roure or DSM under the trademark Parsol 1789, and Merck & Co.under the tradename Eusolex 9020, and Symrise under the tradename NeoHeliopan 357, and has a structure according to the following formula:

In the preferred embodiment of the disclosure, the composition comprisesat least one dibenzoylmethane sunscreen, preferably Avobenzone.

Other types of UVA sunscreens include dicamphor sulfonic acidderivatives, such as ecamsule, a sunscreen sold by Chimex under thetrade name Mexoryl SX, which is terephthalylidene dicamphor sulfonicacid, having the structure according to the following formula:

The composition may contain from about 0.001-20%, preferably about0.005-5%, more preferably about 0.005-3% by weight of the composition ofUVA sunscreen. In the preferred embodiment of the disclosure the UVAsunscreen is Avobenzone, and it is present at not greater than about 3%by weight of the total composition.

2. UVB Chemical Sunscreens

The term “UVB sunscreen” means a compound that blocks UV radiation inthe wavelength range of from about 290 to 320 nm. A variety of UVBchemical sunscreens exist including alpha-cyano-beta, beta-diphenylacrylic acid esters as set forth in U.S. Pat. No. 3,215,724, which ishereby incorporated by reference in its entirety. One particular exampleof an alpha-cyano-beta, beta-diphenyl acrylic acid ester is Octocrylene,which is 2-ethylhexyl 2-cyano-3,3-diphenylacrylate. In certain cases thecomposition may contain no more than about 110% by weight of the totalcomposition of octocrylene. Suitable amounts range from about 0.001-10%by weight. Octocrylene may be purchased from BASF under the tradenameUvinul N-539, from DSM under tradename Parsol 340, and from Symriseunder the tradename Neo Heliopan 303, and has a structure according tothe following formula:

Other suitable sunscreens include benzylidene camphor derivatives as setforth in U.S. Pat. No. 3,781,417, which is hereby incorporated byreference in its entirety. Such benzylidene camphor derivatives have thegeneral formula:

wherein R is p-tolyl or styryl, preferably styryl. Particularlypreferred is 4-methylbenzylidene camphor, which is a lipid soluble UVBsunscreen compound sold under the tradename Eusolex 6300 by Merck, andNeo Heliopan MBC by Symrise, and Parsol 5000 by DSM, having a structureaccording to the following formula:

Also suitable are cinnamate derivatives having the general formula:

wherein R and R₁ are each independently a C₁₋₂₀ straight or branchedchain alkyl. Preferred is where R is methyl and R₁ is a branched chainC₁₋₁₀, preferably C₈ alkyl. The preferred compound is ethylhexylmethoxycinnamate, also referred to as Octinoxate or octylmethoxycinnamate. Octinoxate may be purchased from Givaudan Corporationand DSM under the tradename Parsol MCX, or BASF under the tradenameUvinul MC 80, or Symrise under the tradename Neo Heliopan AV, or Ashlandunder the tradename Escalol 557, having a structure according to thefollowing structure:

Also suitable are mono-, di-, and triethanolamine derivatives of suchmethoxy cinnamates including diethanolamine methoxycinnamate. Cinoxate,the aromatic ether derivative of the above compound is also acceptable.If present, the Cinoxate should be found at no more than about 3% byweight of the total composition.

Also suitable as UVB screening agents are various benzophenonederivatives having the general formula:

wherein R through R⁹ are each independently H, OH, NaO₃S, SO₃H, SO₃Na,Cl, R″, OR″ where R″ is C₁₋₂₀ straight or branched chain alkyl Examplesof such compounds include Benzophenone 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, and 12. Particularly preferred is where the benzophenone derivativeis Benzophenone 3 (also referred to as Oxybenzone), Benzophenone 4 (alsoreferred to as Sulisobenzone), Benzophenone 5 (Sulisobenzone Sodium),and the like. Most preferred is Benzophenone 3, which may be purchasedunder the tradename Uvinul M-40 and NeoHeliopan BB, having the structureaccording to the following formula:

Also suitable are certain menthyl salicylate derivatives having thegeneral formula:

wherein R₁, R₂, R₃, and R₄ are each independently H, OH, NH₂, or C₁₋₂₀straight or branched chain alkyl. Particularly preferred is where R₁,R₂, and R₃ are methyl and R₄ is hydroxyl or NH₂, the compound having thename homomenthyl salicylate (also known as Homosalate) or menthylanthranilate. Menthyl anthranilate is commercially available fromHaarmann & Reimer under the tradename Heliopan. Homosalate is availablecommercially from Merck under the tradename Eusolex HMS, and fromSymrise under the tradename Neo Heliopan HMS, and from DSM under thetradename Parsol HMS, having the structure according to the followingformula:

If present, the Homosalate should be present at no more than about 15%by weight of the total composition.

Various amino benzoic acid derivatives are suitable UVB absorbersincluding those having the general formula:

wherein R₁, R₂, and R₃ are each independently H, C₁₋₂₀ straight orbranched chain alkyl which may be substituted with one or more hydroxygroups. Particularly preferred is wherein R₁ is H or C₁₋₈ straight orbranched alkyl, and R₂ and R₃ are H, or C₁₋₈ straight or branched chainalkyl. Particularly preferred are PABA, ethyl hexyl dimethyl PABA(Padimate O), ethyldihydroxypropyl PABA, and the like. If presentPadimate O should be found at no more than about 8% by weight of thetotal composition.

Salicylate derivatives are also acceptable UVB absorbers. Such compoundshave the general formula: wherein R is a straight or branched chainalkyl, including derivatives of the above compound formed from mono-,di-, or triethanolamines. Particular preferred are octyl salicylate,TEA-salicylate, DEA-salicylate, and mixtures thereof. Octyl salicylatehas the INCI name Ethylhexyl salicylate, and may be purchased fromAshland under the tradename Escalol 587, and Merck under the tradenameEusolex OS, and has the structure according to the following formula:

Generally, the amount of the UVB chemical sunscreen present may rangefrom about 0.001-45%, preferably about 0.005-40%, more preferably about0.01-35% by weight of the total composition.

In one preferred embodiment, the sunscreen may be Avobenzone and/orOctinoxate. It may also be desirable to include one or more othersunscreens in the compositions of the disclosure.

In one preferred embodiment, the composition may be an oil in wateremulsion comprising 5-85% water, 1-40% oil, 0.1-10% Homosalate, 0.1-5%Avobenzone,

If desired, the compositions of the disclosure may be formulated to havea certain SPF (sun protective factor) values ranging from about 1-100,preferably about 4-80, most preferably about 15-60. Calculation of SPFvalues is well known in the art.

3. Other Ingredients:

The topical composition may contain the following ingredients:

Oils

Suitable oils include silicones, esters, vegetable oils, synthetic oils,including but not limited to those set forth herein. The oils may bevolatile or nonvolatile, and are preferably in the form of a pourableliquid at room temperature. If present, the oils may range from about0.5 to 85%, preferably from about 1-75%, more preferably from about5-65% by weight of the total composition.

Cyclic and linear volatile silicones are available from variouscommercial sources including Dow Chemical Corporation and Momentive(formerly General Electric Silicones). The Dow Chemical linear volatilesilicones are sold under the trade names Dowsil and Xiameter 244, 245,344, and 200 fluids. These fluids include hexamethyldisiloxane(viscosity 0.65 centistokes (abbreviated cst)), octamethyltrisiloxane(1.0 cst), decamethyltetrasiloxane (1.5 cst), dodecamethylpentasiloxane(2 cst) and mixtures thereof, with all viscosity measurements being at25° C.

Suitable branched volatile silicones include alkyl trimethicones such asmethyl trimethicone, a branched volatile silicone having the generalformula:

Methyl trimethicone may be purchased from Shin-Etsu Silicones under thetrade name TMF-1.5, having a viscosity of 1.5 centistokes at 25° C.

Also suitable are various straight or branched chain paraffinichydrocarbons having 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, or 20 carbon atoms, more preferably 8 to 16 carbon atoms. Suitablehydrocarbons include pentane, hexane, heptane, decane, dodecane,tetradecane, tridecane, and C₈₋₂₀ isoparaffins. Suitable C₁₂isoparaffins are manufactured by Permethyl Corporation under thetradename Permethyl 99A. Various C₁₆ isoparaffins commerciallyavailable, such as isohexadecane (having the tradename Permethyl R), arealso suitable.

Also suitable are esters formed by the reaction of a carboxylic acid andan alcohol. The alcohol and the carboxylic acids may both have fatty(C6-30) chains. Examples include hexyl laurate, butyl isostearate,hexadecyl isostearate, cetyl palmitate, isostearyl neopentanoate,stearyl heptanoate, isostearyl isononanoate, stearyl lactate, stearyloctanoate, stearyl stearate, isononyl isononanoate, and so on.

The ester may also be in the dimer or trimer form. Examples of suchesters include diisotearyl malate, neopentyl glycol dioctanoate, dibutylsebacate, dicetearyl dimer dilinoleate, dicetyl adipate, diisocetyladipate, diisononyl adipate, diisostearyl dimer dilinoleate,diisostearyl fumarate, diisostearyl malate, dioctyl malate, and so on.

Examples of other types of esters include those from arachidonic,citric, or behenic acids, such as triarachidin, tributyl citrate,triisostearyl citrate, tri C₁₂₋₁₃ alkyl citrate, tricaprylin,tricaprylyl citrate, tridecyl behenate, trioctyldodecyl citrate,tridecyl behenate; or tridecyl cocoate, tridecyl isononanoate, and soon.

Synthetic or naturally occurring glyceryl esters of fatty acids, ortriglycerides, are also suitable for use in the compositions. Bothvegetable and animal sources may be used. Examples of such oils includecastor oil, lanolin oil, C₁₀₋₁₈ triglycerides,caprylic/capric/triglycerides, sweet almond oil, apricot kernel oil,sesame oil, camelina sativa oil, tamanu seed oil, coconut oil, corn oil,cottonseed oil, linseed oil, ink oil, olive oil, palm oil, illipebutter, rapeseed oil, soybean oil, grapeseed oil, sunflower seed oil,walnut oil, and the like.

Also suitable are synthetic or semi-synthetic glyceryl esters, such asfatty acid mono-, di-, and triglycerides which are natural fats or oilsthat have been modified, for example, mono-, di- or triesters of polyolssuch as glycerin. In an example, a fatty (C₁₂₋₂₂) carboxylic acid isreacted with one or more repeating glyceryl groups. glyceryl stearate,diglyceryl diiosostearate, polyglyceryl-3 isostearate, polyglyceryl-4isostearate, polyglyceryl-6 ricinoleate, glyceryl dioleate, glyceryldiisotearate, glyceryl tetraisostearate, glyceryl trioctanoate,diglyceryl distearate, glyceryl linoleate, glyceryl myristate, glycerylisostearate, PEG castor oils, PEG glyceryl oleates, PEG glycerylstearates, PEG glyceryl tallowates, and so on.

Nonvolatile silicone oils, both water soluble and water insoluble, arealso suitable for use in the composition. Such silicones preferably havea viscosity ranging from about greater than 5 to 800,000 cst, preferably20 to 200,000 cst at 25° C. Suitable water insoluble silicones includeamine functional silicones such as amodimethicone. Examples includedimethicone, phenyl dimethicone, diphenyl dimethicone, phenyltrimethicone, or trimethylsiloxyphenyl dimethicone. Other examplesinclude alkyl dimethicones such as cetyl dimethicone, stearyldimethcone, behenyl dimethicone, and the like.

Surfactants

The composition may contain one or more surfactants, especially if inthe emulsion form. However, such surfactants may be used if thecompositions are anhydrous also, and will assist in dispersingingredients that have polarity, for example pigments. Such surfactantsmay be silicone or organic based. The surfactants will aid in theformation of stable emulsions of either the water-in-oil or oil-in-waterform. If present, the surfactant may range from about 0.001 to 30%,preferably from about 0.005 to 25%, more preferably from about 0.1 to20% by weight of the total composition.

Silicone surfactants may be generically referred to as dimethiconecopolyol or alkyl dimethicone copolyol. In some cases the number ofrepeating ethylene oxide or propylene oxide units in the polymer arealso specified, such as a dimethicone copolyol that is also referred toas PEG-15/PPG-10 dimethicone, which refers to a dimethicone havingsubstituents containing 15 ethylene glycol units and 10 propylene glycolunits on the siloxane backbone. It is also possible for one or more ofthe methyl groups in the above general structure to be substituted witha longer chain alkyl (e.g. ethyl, propyl, butyl, etc.) or an ether suchas methyl ether, ethyl ether, propyl ether, butyl ether, and the like.

Examples of silicone surfactants are those sold by Dow Silicones underthe tradename Dowsil 3225C Formulation Aid having the CTFA namecyclotetrasiloxane (and) cyclopentasiloxane (and) PEG/PPG-18dimethicone; or 5225C Formulation Aid, having the CTFA namecyclopentasiloxane (and) PEG/PPG-18/18 dimethicone; or Dowsil 190Surfactant having the CTFA name PEG/PPG-18/18 dimethicone; or Dowsil 193Fluid, Dowsil 5200 having the CTFA name lauryl PEG/PPG-18/18 methicone;or Abil EM 90 having the CTFA name cetyl PEG/PPG-14/14 dimethicone soldby Goldschmidt; or Abil EM 97 having the CTFA name bis-cetylPEG/PPG-14/14 dimethicone sold by Goldschmidt; or Abil WE 09 having theCTFA name cetyl PEG/PPG-10/1 dimethicone in a mixture also containingpolyglyceryl-4 isostearate and hexyl laurate; or KF-6011 sold byShin-Etsu Silicones having the CTFA name PEG-11 methyl etherdimethicone; KF-6012 sold by Shin-Etsu Silicones having the CTFA namePEG/PPG-20/22 butyl ether dimethicone; or KF-6013 sold by Shin-EtsuSilicones having the CTFA name PEG-9 dimethicone; or KF-6015 sold byShin-Etsu Silicones having the CTFA name PEG-3 dimethicone; or KF-6016sold by Shin-Etsu Silicones having the CTFA name PEG-9 methyl etherdimethicone; or KF-6017 sold by Shin-Etsu Silicones having the CTFA namePEG-10 dimethicone; or KF-6038 sold by Shin-Etsu Silicones having theCTFA name lauryl PEG-9 poly dimethylsiloxyethyl dimethicone.

Also suitable are various types of crosslinked silicone surfactants thatare often referred to as emulsifying elastomers that contain at leastone hydrophilic moiety such as polyoxy alkylenated groups.Polyoxyalkylenated silicone elastomers that may be used in at least oneembodiment of the disclosure include those sold by Shin-Etsu Siliconesunder the names KSG-21, KSG-20, KSG-30, KSG-31, KSG-32, KSG-33; KSG-210which is dimethicone/PEG-10/15 crosspolymer dispersed in dimethicone;KSG-310 which is PEG-15 lauryl dimethicone crosspolymer; KSG-320 whichis PEG-15 lauryl dimethicone crosspolymer dispersed in isododecane;KSG-330 (the former dispersed in triethylhexanoin), KSG-340 which is amixture of PEG-10 lauryl dimethicone crosspolymer and PEG-15 lauryldimethicone crosspolymer.

Also suitable are polyglycerolated silicone elastomers like thosedisclosed in PCT/WO 2004/024798, which is hereby incorporated byreference in its entirety. Such elastomers include Shin-Etsu's KSGseries, such as KSG-710 which is dimethicone/polyglycerin-3 crosspolymerdispersed in dimethicone; or lauryl dimethicone/polyglycerin-3crosspolymer dispersed in a variety of solvent such as isododecane,dimethicone, triethylhexanoin, sold under the Shin-Etsu tradenamesKSG-810, KSG-820, KSG-830, or KSG-840. Also suitable are silicones soldby Dow Silicones under the tradenames 9010 and DC9011.

The composition may comprise one or more nonionic organic surfactants.Suitable nonionic surfactants include alkoxylated alcohols, or ethers,formed by the reaction of an alcohol with an alkylene oxide, usuallyethylene or propylene oxide. Preferably the alcohol is either a fattyalcohol having 6 to 30 carbon atoms. Examples of such ingredientsinclude Steareth 2-100, which is formed by the reaction of stearylalcohol and ethylene oxide and the number of ethylene oxide units rangesfrom 2 to 100; Beheneth 5-30 which is formed by the reaction of behenylalcohol and ethylene oxide where the number of repeating ethylene oxideunits is 5 to 30; Ceteareth 2-100, formed by the reaction of a mixtureof cetyl and stearyl alcohol with ethylene oxide, where the number ofrepeating ethylene oxide units in the molecule is 2 to 100; Ceteth 1-45which is formed by the reaction of cetyl alcohol and ethylene oxide, andthe number of repeating ethylene oxide units is 1 to 45, and so on. Allrecitations of units include all whole integers between the range.

Other alkoxylated alcohols are formed by the reaction of fatty acids andmono-, di- or polyhydric alcohols with an alkylene oxide. For example,the reaction products of C₆₋₃₀ fatty carboxylic acids and polyhydricalcohols which are monosaccharides such as glucose, galactose, methylglucose, and the like, with an alkoxylated alcohol. Examples includepolymeric alkylene glycols reacted with glyceryl fatty acid esters suchas PEG glyceryl oleates, PEG glyceryl stearate; or PEGpolyhydroxyalkanotes such as PEG dipolyhydroxystearate wherein thenumber of repeating ethylene glycol units ranges from 3 to 1000.

Other suitable nonionic surfactants include alkoxylated sorbitan andalkoxylated sorbitan derivatives. For example, alkoxylation, inparticular ethoxylation of sorbitan provides polyalkoxylated sorbitanderivatives. Esterification of polyalkoxylated sorbitan providessorbitan esters such as the polysorbates. For example, thepolyalkyoxylated sorbitan can be esterified with C₆₋₃₀, preferablyC₁₂₋₂₂ fatty acids. Examples of such ingredients include Polysorbates20-85, sorbitan oleate, sorbitan sesquioleate, sorbitan palmitate,sorbitan sesquiisostearate, sorbitan stearate, and so on.

Humectants

It may also be desirable to include one or more humectants in thecomposition. If present, such humectants may range from about 0.001 to25%, preferably from about 0.005 to 20%, more preferably from about 0.1to 15% by weight of the total composition. Examples of suitablehumectants include glycols, sugars, and the like. Suitable glycols arein monomeric or polymeric form and include polyethylene andpolypropylene glycols such as PEG 4-200, which are polyethylene glycolshaving from 4 to 200 repeating ethylene oxide units; as well as C₁₋₆alkylene glycols such as propylene glycol, butylene glycol, pentyleneglycol, and the like. Suitable sugars, some of which are also polyhydricalcohols, are also suitable humectants. Examples of such sugars includeglucose, fructose, honey, hydrogenated honey, inositol, maltose,mannitol, maltitol, sorbitol, sucrose, xylitol, xylose, and so on. Alsosuitable is urea. Preferably, the humectants used in the composition ofthe disclosure are C₁₋₆, preferably C₂₋₄ alkylene glycols, mostparticularly butylene glycol.

Botanical Extracts

It may be desirable to include one or more botanical extracts in thecompositions. If so, suggested ranges are from about 0.0001 to 10%,preferably about 0.0005 to 8%, more preferably about 0.001 to 5% byweight of the total composition. Suitable botanical extracts includeextracts from plants (herbs, roots, flowers, fruits, seeds) such asflowers, fruits, vegetables, and so on, including yeast ferment extract,Padina Pavonica extract, Thermus thermophilis ferment extract, camelinasativa seed oil, boswellia serrata extract, olive extract, AribodopsisThaliana extract, Acacia Dealbata extract, Acer Saccharinum (sugarmaple), acidopholus, acorus, aesculus, agaricus, agave, agrimonia,algae, aloe, citrus, brassica, cinnamon, orange, apple, blueberry,cranberry, peach, pear, lemon, lime, pea, seaweed, caffeine, green tea,chamomile, willowbark, mulberry, poppy, and those set forth on pages1646 through 1660 of the CTFA Cosmetic Ingredient Handbook, EighthEdition, Volume 2. Further specific examples include, but are notlimited to, Glycyrrhiza Glabra, Salix Nigra, Macrocycstis Pyrifera,Pyrus Malus, Saxifraga Sarmentosa, Vitis Vinifera, Morus Nigra,Scutellaria Baicalensis, Anthemis Nobilis, Salvia Sclarea, RosmarinusOfficianalis, Citrus Medica Limonum, Panax Ginseng, SiegesbeckiaOrientalis, Fructus Mume, Ascophyllum Nodosum, Bifida Ferment lysate,Glycine Soja extract, Beta Vulgaris, Haberlea Rhodopensis, PolygonumCuspidatum, Citrus Aurantium Dulcis, Vitis Vinifera, SelaginellaTamariscina, Humulus Lupulus, Citrus Reticulata Peel, Punica Granatum,Asparagopsis, Curcuma Longa, Menyanthes Trifoliata, Helianthus Annuus,Hordeum Vulgare, Cucumis Sativus, Evernia Prunastri, Evernia Furfuracea,and mixtures thereof.

Particulate Materials

The compositions of the disclosure may contain particulate materials inthe form of pigments, inert particulates, or mixtures thereof. Ifpresent, suggested ranges are from about 0.01-75%, preferably about0.5-70%, more preferably about 0.1-65% by weight of the totalcomposition. In the case where the composition may comprise mixtures ofpigments and powders, suitable ranges include about 0.01-75% pigment and0.1-75% powder, such weights by weight of the total composition.

The particulate matter may be colored or non-colored powders. Suitablenon-pigmented powders include bismuth oxychloride, titanated mica, fumedsilica, spherical silica, polymethylmethacrylate, micronized teflon,boron nitride, acrylate copolymers, aluminum silicate, aluminum starchoctenylsuccinate, bentonite, calcium silicate, cellulose, chalk, cornstarch, diatomaceous earth, fuller's earth, glyceryl starch, hectorite,hydrated silica, kaolin, magnesium aluminum silicate, magnesiumtrisilicate, maltodextrin, montmorillonite, microcrystalline cellulose,rice starch, silica, talc, mica, titanium dioxide, zinc laurate, zincmyristate, zinc rosinate, alumina, attapulgite, calcium carbonate,calcium silicate, dextran, kaolin, nylon, silica silylate, silk powder,sericite, soy flour, tin oxide, titanium hydroxide, trimagnesiumphosphate, walnut shell powder, or mixtures thereof. The above mentionedpowders may be surface treated with lecithin, amino acids, mineral oil,silicone, or various other agents either alone or in combination, whichcoat the powder surface and render the particles more lipophilic innature.

Suitable pigments are organic or inorganic. Organic pigments aregenerally various aromatic types including azo, indigoid,triphenylmethane, anthroquinone, and xanthine dyes which are designatedas D&C and FD&C blues, browns, greens, oranges, reds, yellows, etc.Organic pigments generally consist of insoluble metallic salts ofcertified color additives, referred to as the Lakes. Inorganic pigmentsinclude iron oxides, ultramarines, chromium, chromium hydroxide colors,and mixtures thereof. Iron oxides of red, blue, yellow, brown, black,and mixtures thereof are suitable.

Vitamins and Antioxidants

The compositions of the disclosure may contain vitamins and/orcoenzymes, as well as antioxidants. If so, 0.001-10%, preferably0.01-8%, more preferably 0.05-5% by weight of the total composition issuggested. Suitable vitamins include ascorbic acid and derivativesthereof such as ascorbyl palmitate, tetrahexydecyl ascorbate, and so on;the B vitamins such as thiamine, riboflavin, pyridoxin, and so on, aswell as coenzymes such as thiamine pyrophoshate, flavin adenindinucleotide, folic acid, pyridoxal phosphate, tetrahydrofolic acid, andso on. Also suitable is Vitamin E and derivatives thereof such asVitamin E acetate, nicotinate, or other esters thereof. In addition,Vitamins D and K are suitable.

C. The Methods

In some embodiments, the disclosure is related to methods forstabilizing photoactive compounds, the methods comprise mixing a leastone photoactive compound with at least one heterocyclic compound havingthe structure according to Formula I.

In one aspect, the methods for stabilizing retinoids and derivativesthereof comprise mixing a least one retinoid and/or derivatives thereofwith at least one heterocyclic compound having the structure accordingto Formula I.

In one aspect, the methods for stabilizing chemical sunscreens comprisemixing a least one chemical sunscreen with at least one heterocycliccompound having the structure according to Formula I.

The disclosure will be further described in connection with thefollowing examples which are set forth for the purposes of illustrationonly.

EXPERIMENTAL Compound Examples Example 1 Synthesis of Compound 1

1,8-Diazaanthraquinone (6 gm, 28.5 mmol) and toluene (40 mL) are mixedin a clean 250 mL 2 neck round bottom flask equipped with Dean-Starkcondenser and nitrogen inlet. 2-Ethylhexyl cyanoacetate (4.4 gm, 22.3mmol), ammonium acetate (153 mg, 2.0 mmol), and acetic acid (2.8 mL) areadded sequentially at 25-30° C. The reaction mixture is refluxed forapproximately 18 hours at 100-115° C. The water is periodically removedfrom Dean-Stark condenser during the reaction. The reaction is monitoredby TLC (ethyl acetate/hexane). After the complete consumption of1,8-diazaanthraquinone by TLC, the reaction mixture is cooled to roomtemperature. The toluene layer is washed with water (2×25 mL) followedby saturated sodium bicarbonate solution (25 mL) and again with water(25 mL). The organic layer is evaporated under reduced pressure at45-50° C. to obtain crude product as pale brown semisolid. The crudeproduct is purified by column chromatography by eluting with ethylacetate in hexane to afford pure product.

Example 2 Synthesis of Compound 2

1,5-Diazaanthraquinone (6 gm, 28.5 mmol) and toluene (40 mL) are mixedin a clean 250 mL 2 neck round bottom flask equipped with Dean-Starkcondenser and nitrogen inlet. 2-Ethylhexyl cyanoacetate (4.4 gm, 22.3mmol), ammonium acetate (153 mg, 2.0 mmol), and acetic acid (2.8 mL) areadded sequentially at 25-30° C. The reaction mixture is refluxed forapproximately 18 hours at 100-115° C. The water is periodically removedfrom Dean-Stark condenser during the reaction. The reaction is monitoredby TLC (ethyl acetate/hexane). After the complete consumption of1,5-diazaanthraquinone by TLC, the reaction mixture is cooled to roomtemperature. The toluene layer is washed with water (2×25 mL) followedby saturated sodium bicarbonate solution (25 mL) and again with water(25 mL). The organic layer is evaporated under reduced pressure at45-50° C. to obtain crude product as pale brown semisolid. The crudeproduct is purified by column chromatography by eluting with ethylacetate in hexane to afford pure product.

Example 3 Synthesis of Compound 3

1-Azaanthraquinone (6 gm, 28.5 mmol) and toluene (40 mL) are mixed in aclean 250 mL 2 neck round bottom flask equipped with Dean-Starkcondenser and nitrogen inlet. 2-Ethylhexyl cyanoacetate (4.4 gm, 22.3mmol), ammonium acetate (153 mg, 2.0 mmol), and acetic acid (2.8 mL) areadded sequentially at 25-30° C. The reaction mixture is refluxed forapproximately 18 hours at 100-115° C. The water is periodically removedfrom Dean-Stark condenser during the reaction. The reaction is monitoredby TLC (ethyl acetate/hexane). After the complete consumption of1-azaanthraquinone by TLC, the reaction mixture is refluxed cooled toroom temperature. The toluene layer is washed with water (2×25 mL)followed by saturated sodium bicarbonate solution (25 mL) and again withwater (25 mL). The organic layer is evaporated under reduced pressure at45-50° C. to obtain crude product as pale brown semisolid. The crudeproduct is purified by column chromatography by eluting with ethylacetate in hexane to afford pure product.

Example 4 Synthesis of Compound 4

1,3,5,7-Tetraazaanthraquinone (6 gm, 28.5 mmol) and toluene (40 mL) aremixed in a clean 250 mL 2 neck round bottom flask equipped withDean-Stark condenser and nitrogen inlet. 2-Ethylhexyl cyanoacetate (4.4gm, 22.3 mmol), ammonium acetate (153 mg, 2.0 mmol), and acetic acid(2.8 mL) are added sequentially at 25-30° C. The reaction mixture isrefluxed for approximately 18 hours at 100-115° C. The water isperiodically removed from Dean-Stark condenser during the reaction. Thereaction is monitored by TLC (ethyl acetate/hexane). After the completeconsumption of 1,3,5,7-tetraazaanthraquinone by TLC, the reactionmixture is refluxed cooled to room temperature. The toluene layer iswashed with water (2×25 mL) followed by saturated sodium bicarbonatesolution (25 mL) and again with water (25 mL). The organic layer isevaporated under reduced pressure at 45-50° C. to obtain crude productas pale brown semisolid. The crude product is purified by columnchromatography by eluting with ethyl acetate in hexane to afford pureproduct.

Example 5 Synthesis of Compound 5

1,3-Diazaanthraquinone (6 gm, 28.5 mmol) and toluene (40 mL) are mixedin a clean 250 mL 2 neck round bottom flask equipped with Dean-Starkcondenser and nitrogen inlet. 2-Ethylhexyl cyanoacetate (4.4 gm, 22.3mmol), ammonium acetate (153 mg, 2.0 mmol), and acetic acid (2.8 mL) areadded sequentially at 25-30° C. The reaction mixture is refluxed forapproximately 18 hours at 100-115° C. The water is periodically removedfrom Dean-Stark condenser during the reaction. The reaction is monitoredby TLC (ethyl acetate/hexane). After the complete consumption of1,3-diazaanthraquinone by TLC, the reaction mixture is refluxed cooledto room temperature. The toluene layer is washed with water (2×25 mL)followed by saturated sodium bicarbonate solution (25 mL) and again withwater (25 mL). The organic layer is evaporated under reduced pressure at45-50° C. to obtain crude product as pale brown semisolid. The crudeproduct is purified by column chromatography by eluting with ethylacetate in hexane to afford pure product.

Example 6 Synthesis of Compound 6

1,8-Diazaanthraquinone (2 gm, 9.5 mmol) and toluene (40 mL) are mixed ina clean 250 mL 2 neck round bottom flask equipped with Dean-Starkcondenser and nitrogen inlet. 2-Ethylhexyl cyanoacetate (4.4 gm, 22.3mmol), ammonium acetate (153 mg, 2.0 mmol), and acetic acid (2.8 mL) areadded sequentially at 25-30° C. The reaction mixture is refluxed forapproximately 18 hours at 100-115° C. The water is periodically removedfrom Dean-Stark condenser during the reaction. The reaction is monitoredby TLC (ethyl acetate/hexane). After the complete consumption of1,8-diazaanthraquinone by TLC, the reaction mixture is refluxed foranother 12 hours and then cooled to room temperature. The toluene layeris washed with water (2×25 mL) followed by saturated sodium bicarbonatesolution (25 mL) and again with water (25 mL). The organic layer isevaporated under reduced pressure at 45-50° C. to obtain crude productas pale brown semisolid. The crude product is purified by colunmchromatography by eluting with ethyl acetate in hexane to afford pureproduct.

Example 7 Synthesis of Compound 7

1,5-Diazaanthraquinone (2 gm, 9.5 mmol) and toluene (40 mL) are mixed ina clean 250 mL 2 neck round bottom flask equipped with Dean-Starkcondenser and nitrogen inlet. 2-Ethylhexyl cyanoacetate (4.4 gm, 22.3mmol), ammonium acetate (153 mg, 2.0 mmol), and acetic acid (2.8 mL) areadded sequentially at 25-30° C. The reaction mixture is refluxed forapproximately 18 hours at 100-115° C. The water is periodically removedfrom Dean-Stark condenser during the reaction. The reaction is monitoredby TLC (ethyl acetate/hexane). After the complete consumption of1,5-diazaanthraquinone by TLC, the reaction mixture is refluxed foranother 12 hours and then cooled to room temperature. The toluene layeris washed with water (2×25 mL) followed by saturated sodium bicarbonatesolution (25 mL) and again with water (25 mL). The organic layer isevaporated under reduced pressure at 45-50° C. to obtain crude productas pale brown semisolid. The crude product is purified by columnchromatography by eluting with ethyl acetate in hexane to afford pureproduct.

Example 8 Synthesis of Compound 8

1-Azaanthraquinone (2 gm, 9.5 mmol) and toluene (40 mL) are mixed in aclean 250 mL 2 neck round bottom flask equipped with Dean-Starkcondenser and nitrogen inlet. 2-Ethylhexyl cyanoacetate (4.4 gm, 22.3mmol), ammonium acetate (153 mg, 2.0 mmol), and acetic acid (2.8 mL) areadded sequentially at 25-30° C. The reaction mixture is refluxed forapproximately 18 hours at 100-115° C. The water is periodically removedfrom Dean-Stark condenser during the reaction. The reaction is monitoredby TLC (ethyl acetate/hexane). After the complete consumption of1-azaanthraquinone by TLC, the reaction mixture is refluxed for another12 hours and then cooled to room temperature. The toluene layer iswashed with water (2×25 mL) followed by saturated sodium bicarbonatesolution (25 mL) and again with water (25 mL). The organic layer isevaporated under reduced pressure at 45-50° C. to obtain crude productas pale brown semisolid. The crude product is purified by columnchromatography by eluting with ethyl acetate in hexane to afford pureproduct.

Example 9 Synthesis of Compound 9

1,3,5,7-Tetraazaanthraquinone (2 gm, 9.5 mmol) and toluene (40 mL) aremixed in a clean 250 mL 2 neck round bottom flask equipped withDean-Stark condenser and nitrogen inlet. 2-Ethylhexyl cyanoacetate (4.4gm, 22.3 mmol), ammonium acetate (153 mg, 2.0 mmol), and acetic acid(2.8 mL) are added sequentially at 25-30° C. The reaction mixture isrefluxed for approximately 18 hours at 100-115° C. The water isperiodically removed from Dean-Stark condenser during the reaction. Thereaction is monitored by TLC (ethyl acetate/hexane). After the completeconsumption of 1,3,5,7-tetraazaanthraquinone by TLC, the reactionmixture is refluxed for another 12 hours and then cooled to roomtemperature. The toluene layer is washed with water (2×25 mL) followedby saturated sodium bicarbonate solution (25 mL) and again with water(25 mL). The organic layer is evaporated under reduced pressure at45-50° C. to obtain crude product as pale brown semisolid. The crudeproduct is purified by column chromatography by eluting with ethylacetate in hexane to afford pure product.

Example 10 Synthesis of Compound 10

1,3-Diazaanthraquinone (2 gm, 9.5 mmol) and toluene (40 mL) are mixed ina clean 250 mL 2 neck round bottom flask equipped with Dean-Starkcondenser and nitrogen inlet. 2-Ethylhexyl cyanoacetate (4.4 gm, 22.3mmol), ammonium acetate (153 mg, 2.0 mmol), and acetic acid (2.8 mL) areadded sequentially at 25-30° C. The reaction mixture is refluxed forapproximately 18 hours at 100-115° C. The water is periodically removedfrom Dean-Stark condenser during the reaction. The reaction is monitoredby TLC (ethyl acetate/hexane). After the complete consumption of1,3-diazaanthraquinone by TLC, the reaction mixture is refluxed foranother 12 hours and then cooled to room temperature. The toluene layeris washed with water (2×25 mL) followed by saturated sodium bicarbonatesolution (25 mL) and again with water (25 mL). The organic layer isevaporated under reduced pressure at 45-50° C. to obtain crude productas pale brown semisolid. The crude product is purified by columnchromatography by eluting with ethyl acetate in hexane to afford pureproduct.

Composition Examples Example 11

An anti-aging cream is prepared as follows:

Ingredient Wt % Water QS100 Shea butter 6.00Caprylic/capric/myristic/stearic 5.50 triglyceride Methyl trimethicone5.00 Di-C12-15 alkyl fumarate 4.00 Dimethicone/polysilicone-11 4.00Butylene glycol 3.00 Steareth-2 2.30 Glyceryl stearate 1.50 Pentyleneglycol 1.50 Stearyl alcohol 1.50 Steareth-21 1.20 Glycerin 1.00 Phenoxyethanol 0.50 Acrylamide/sodium 0.50 acryloyldimethyltauratecopolymer/water/isohexadecane/ polysorbate 80 Fragrance 0.40 Carbomer0.35 Water/sodium hydroxide 0.28 Cholesterol 0.20 Linoleic acid 0.20Caffeine 0.20 Dimethicone 0.20 Sodium dehydroacetate 0.10 Tocopherolacetate 0.10 Compound 1 0.50

The composition is prepared by separately mixing the oil phaseingredients including the Compound 1. The water phase ingredients arecombined and emulsified with the oil phase ingredients to form anemulsion.

Example 12

A formula with stabilized retinol is prepared as follows:

Ingredient Wt % Water QS100 Butylene glycol 1.60 Sodium bisulfite 0.02Caffeine 0.20 Silica 0.20 Caprylic/capric triglyceride 3.17 Dimethicone3.00 Cetearyl alcohol 2.00 Tocopheryl acetate 0.50 Tocopherol 0.20Disodium EDTA 0.10 Sodium hyaluronate 0.10 Cholesterol 0.20 Arachidylalcohol 1.37 Polysorbate 60 0.03 Behenyl alcohol 0.75 Sodium hydroxide0.07 Hydroxy ethylcellulose 0.30 Retinol 0.30 Stearyl dimethicone 2.25Caprylyl glycol 0.32 Glycerin 2.50 Shea butter 2.80 Sorbitan olivate0.80 Sorbitan isostearate 0.03 Cetearyl olivate 1.20 Arachidyl glucoside0.38 PEG-12 dimethicone/PPG-20 crosspolymer 1.60 Compound 1 0.15

The composition is prepared by separately combining the water phase andoil phase with the Compound 1. The phases are mixed to emulsify and forma lotion.

Example 13

A sunscreen composition containing Compound 1 is prepared as follows:

Phase Ingredient Wt % A Deionized water QS100 B Glycerin 2.50 BTriethanolamine 0.60 B Disodium EDTA 0.10 C Compound 1 2.00 CDimethicone (2 cs) 2.00 C Glyceryl stearate/PEG 100 stearate 2.50 CBeeswax 1.00 D Avobenzone 3.00 D Homosalate 10.00 D Octisalate 5.00 DOctocrylene 4.00 F Dimethicone/Acrylates dimethicone copolymer 2.50 FTrimethylsiloxysilicate/dimethicone 2.50 GAmmonium/Acryloyldimethyltaurate copolymer 0.50 H Caprylylglycol/phenoxyethanol/hexylene glycol 1.00

The Phase A ingredients are charged into a main kettle. Phase Bingredients are added and propeller mixed at medium/high speed untilhomogeneous. The batch is then heated to a temperature of 67-70° C. Inan auxiliary kettle the Phase C ingredients are heated to 65-70° C. andmixed with a propeller at medium speed. The Phase D ingredients areadded and mixing at medium speed continued until uniform. The heat islowered to 63° C. and the Phase E ingredients are added into the vortexwith propeller mixing until dispersed. Phases C, D, and E are added intothe main batch (A+B) while mixing at high speed. The composition ishomogenized at 2000 rpm for 15-20 minutes. When the batch is emulsifiedand homogeneous, propeller mixing is continued and pre-mixed Phase Fingredients are added and mixed until uniform while cooling the batch toroom temperature. Phases G and H are then added and mixed until uniform.The batch is cooled to room temperature.

Other Embodiments

While the invention has been described in connection with the preferredembodiment, it is not intended to limit the scope of the invention tothe particular form set forth but, on the contrary, it is intended tocover such alternatives, modifications, and equivalents as may beincluded within the spirit and scope of the invention as defined by theappended claims. Therefore, other embodiments, including those can beeasily modified by a person skilled in the art from the presentdisclosure, are also within the claims.

The invention claimed is:
 1. A heterocyclic compound selected from thegroup consisting of:

and mixtures thereof.
 2. A composition comprising at least oneheterocyclic compound of claim
 1. 3. The composition of claim 2, whereinthe heterocyclic compound is present in amount ranging from 0.01 to 25%by weight of the total composition.
 4. The composition of claim 2,further comprising at least one photoactive compound.
 5. The compositionof claim 4, wherein the photoactive compound is selected from the groupconsisting of a retinoid, a sunscreen, or mixture thereof.
 6. Thecomposition of claim 5, wherein the photoactive compound is a retinoid.7. The composition of claim 6, wherein the retinoid is present in amountranging from about 0.0001 to about 20% by weight of the totalcomposition.
 8. The composition of claim 5, wherein the photoactivecompound is a sunscreen.
 9. The composition of claim 8, wherein thesunscreen is selected from the group consisting of a UVA chemicalsunscreen, a UVB chemical sunscreen, a physical sunscreen, and mixturethereof.
 10. The composition of claim 9, wherein the sunscreen is a UVAchemical sunscreen.
 11. The composition of claim 10, wherein the UVAchemical sunscreen is present in amount ranging from about 0.001 toabout 20% by weight of the total composition.
 12. The composition ofclaim 9, wherein the sunscreen is a UVB chemical sunscreen.
 13. Thecomposition of claim 12, wherein the UVB chemical sunscreen is presentin amount ranging from about 0.001 to about 45% by weight of the totalcomposition.
 14. The composition of claim 4, further comprising at leastone ingredient selected from the group consisting of oils, surfactants,humectants, botanical extracts, particulate materials, antioxidants, andother vitamins.